Neoadjuvant chemotherapy in high‐risk soft tissue sarcomas: A Sarculator‐based risk stratification analysis of the ISG‐STS 1001 randomized trial

Abstract

Background The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS. Methods This study analyzed data from ISG‐STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology‐tailored (HT) chemotherapy in adult patients with STS. The 10‐year predicted overall survival (pr‐OS) was estimated with the Sarculator and was stratified into higher (10‐year pr‐OS < 60%) and lower risk subgroups (10‐year pr‐OS ≥ 60%). Results The median pr‐OS was 0.63 (interquartile range [IQR], 0.51‐0.72) for the entire study population, 0.62 (IQR, 0.51‐0.70) for the AI arm, and 0.64 (IQR, 0.51‐0.73) for the HT arm. Three‐ and 5‐year overall survival (OS) were 0.86 (95% confidence interval [CI], 0.82‐0.93) and 0.81 (95% CI, 0.71‐0.86) in lower risk patients and 0.69 (95% CI, 0.70‐0.85) and 0.59 (95% CI, 0.51‐0.72) in the higher risk patients (log‐rank test, P = .004). In higher risk patients, the 3‐ and 5‐year Sarculator‐predicted and study‐observed OS rates were 0.68 and 0.58, respectively, and 0.85 and 0.66, respectively, in the AI arm (P = .04); the corresponding figures in the HT arm were 0.69 and 0.60, respectively, and 0.69 and 0.55, respectively (P > .99). In lower risk patients, the 3‐ and 5‐year Sarculator‐predicted and study‐observed OS rates were 0.85 and 0.80, respectively, and 0.89 and 0.82, respectively, in the AI arm (P = .507); the corresponding figures in the HT arm were 0.87 and 0.81, respectively, and 0.86 and 0.74, respectively (P = .105). Conclusions High‐risk patients treated with AI performed better than predicted, and this adds to the evidence for the efficacy of neoadjuvant AI in STS. Lay Summary People affected by soft tissue sarcomas of the extremities and trunk wall are at some risk of developing metastasis after surgery. Preoperative or postoperative chemotherapy has been tested in clinical trials to reduce the chances of distant metastasis. However, study findings have not been conclusive. This study stratified the risk of metastasis for people affected by sarcomas who were included in a clinical trial testing neoadjuvant chemotherapy. Exploiting the prognostic nomogram Sarculator, it found a benefit for chemotherapy when the predicted risk, based on patient and tumor characteristics, was high.

Prediction tools for the personalized management of soft-tissue sarcomas of the extremity

“…23,25,26 Recent studies have shown improved survival for patients treated with anthracycline-and ifosfamide-based chemotherapy in localized eSTSs in high-risk patients. [33][34][35] These patients were identified using prediction tools, which anticipate individual risks of metastasis formation and death based on characteristics of the patient, tumour, and treatment. 36,37 A survey among sarcoma specialists reported that 81% consider the use of a prediction tool for the indication of (neo)adjuvant chemotherapy in patients with a primary eSTS, 12 marking a recent trend to a more patient-tailored approach in the management of these tumours.…”

The role of perioperative chemotherapy in primary high-grade extremity soft tissue sarcoma: A risk-stratified analysis using PERSARC

“…A recent posthoc subgroup analysis of this trial showed a beneficial effect (HR 0.50) of AI-based CTX in a small subgroup of patients with a predicted 10-year OS of 60% based on the prognostic nomogram Sarculator [4]. In addition, another study found a 5-year OS of 66% in a subgroup of patients who received AI-based CTX with a predicted 10year OS of 60% based on the Sarculator [6]. These findings are comparable with our results, in which we found a HR of 0.66 for AI-based CTX with a 5-year OS of 70% in the AI-based CTX group and 59% in the no CTX group in the high PERSARC-risk population with a predicted 5-year OS of 66%.…”

Therapeutic perspectives for adult soft tissue sarcoma—updates from the 2022 ASCO annual meeting

“…Meanwhile, trabectedin showed a better safety profile with much less hematological toxicity and slightly increased liver toxicity, which was primarily grade 1 or 2 2 . Moreover, neoadjuvant chemotherapy conferred an OS benefit for patients with MLPS, compared with the survival threshold predicted by the nomogram in the validated Sarculator tool 3 .…”